Advances in treatment research: summary of the NIH/HHS videocast

In honor of Autism Awareness month, the National Institutes of Health in conjunction with the Department of Health and Human Services held an hour-long lecture and live videocast with two seasoned autism researchers. The talk series was titled “Advances in Treatment Research” and addressed the current state of treatment research in autism including promising new areas and the barriers to getting to effective treatments faster.

Susan Swedo, M.D., a board-certified pediatrician and the Chief of the Pediatrics & Developmental Neuropsychiatry Branch at the National Institute of Mental Health (NIMH), spoke about empirically-supported treatment options in autism, including behavioral and medical treatments. She noted that methods of behavioral intervention have been the most studied. A recent review published in Pediatrics highlighted the positive effects demonstrated in randomized controlled trials of early intervention, including the UCLA Lovass model and the Early Start Denver model of early intervention.

For medical interventions aimed at addressing core symptoms of ASD, such as social and communication impairments, the challenge of evaluating treatments has been greater. Objectively measuring improvements in social and communication is challenging because these impairments differ widely across individuals with ASD. For example, for some the difficulty may be establishing eye contact whereas for others it might be learning how to carry on a conversation. Thus, defining what makes a treatment successful has been surprisingly elusive. For medical conditions where someone became acutely ill, a return to that individual’s former health status would be considered a success. However, autism spectrum disorders are developmental in nature, and difficulties in meeting milestones and acquiring new information about the world tend to compound. For these reasons, it is not clear what the “baseline” is or could be for each individual and that makes the definition of success less clear-cut. This is an even greater concern when considering the costs of treatment, including monetary and potential side effects. For an intervention with a high probability of unpleasant side effects, the likelihood of substantial gain in function must be greater than for an intervention with little risk of negative effects.

Secondly, there appears to be a surprisingly strong placebo effect in autism studies. For some individuals, the psychological effect of receiving “treatment”—even if it is not an active substance– is beneficial in some way. For this reason, small and uncontrolled trials of interventions can be misleading. Large, randomized, controlled trials are considered to be the gold standard method for evaluating effective treatments. Another challenge is that, given that ASD is not one condition but a group of different conditions, what will work for one person may not work for another. When individuals are studied in groups, such as in clinical trials, it might obscure the positive effects of a treatment for a small subgroup of people with ASD.

Dr. Swedo offered the historical example of secretin as a case-in-point. Secretin is a hormone that was claimed to be a successful treatment for autism in many “open label” (ie. uncontrolled) trials. The hormone was both very expensive and difficult to administer. When placebo-controlled trials were completed, it was clear that there weren’t beneficial effect of the drug, but valuable treatment time and dollars were spent on something ineffective in the interim.

Dr. Swedo collaborates with Autism Speaks’ Autism Treatment Network, a group of 17 hospitals offering a comprehensive model of medical care for children on the spectrum. The well-organized network of sites offers an excellent platform for studies of medical effectiveness where the children’s medical needs are well-attended and followed over time.

Dr. Swedo’s talk ended by discussing some new data from her research group at NIMH showing that the sleep EEG patterns of children with autism are different in a surprising way. Young children with autism in her study spend much less time in rapid eye movement (REM) sleep and much greater time in slow wave sleep instead. This is an interesting finding because REM sleep has been hypothesized as important for consolidating memories made during waking hours. Dr. Swedo’s group is currently engaged in the beginning phases of a study using a low dose of Aricept, a drug indicated for dementia associated with Alzheimer’s disease that has the side effect of increasing REM sleep. Autism Speaks is currently funding a study that is examining the relationship between REM sleep and other aspects of sleep and memory in children with ASD. We look forward to hearing the results as they emerge.

Rebecca Landa, Ph.D., CCC-SLP, is an Associate Professor of Psychiatry and Johns Hopkins School of Medicine and Director of the Center for Autism and Related Disorders and of the REACH research program at the Kennedy Krieger Institute. Dr. Landa explores the early signs and interventions for autism during the infant-toddler period.

Dr. Landa views early intervention as “an investment of a lifetime”, because it is during this early time that children set expectations and learn what they are capable of, and the dynamic of the parent-child relationship is established. Her objective in all interventions is to “thwart the spiraling effects” of developmental disorders by improving functioning as quickly as possible.

“I like to think of intervention experience as nourishment for the brain”, says Dr. Landa. New experiences help young children learn how to functionally interact with the world. As young children, the sensory and motor abilities are primary and help set up more complex cognitive and social skills. A good example is in the ‘sticky mittens’ Dr. Amy Needham uses to help young infants learn to grasp. With the special mittens, the young infants had success at a motor skill that they could not previously perform, and this provided a scaffold for building other behaviors. Dr. Landa’s interventions are influenced by the perspective that the mind develops in a manner compelled by the physical abilities and actions of the body.

Dr. Landa also described a randomized controlled behavioral intervention for 16 month old children who have autism or were at high risk for developing autism. Some of the children were randomized into an intensive parent education class to help the parents have more effective interactions with their infants. Other children were enrolled in a full experimental treatment group, involving a classroom-based gathering of one year olds and their parents twice a week. In the experimental group parents learn to observe and implement strategies for engaging their children socially, with toys, and in adaptive routines that help parents generalize to the home through weekly home visits. The children in the experimental group made substantial improvements in their gaze behavior, spending more time engaged in the sort of joint attention interactions that precede more complex social interactions. Meeting these early milestones offer the scaffold for the development of later and more complex social and communicative behaviors.

In addition to their prepared talks, both investigators answered questions from the live audience. The videocast will be archived and available for viewing in the next few days.

There is a disconnect in this story. If “what will work for one person may not work for another,” then why use controlled trials that mask such individual benefit? The secretin story proves the point. Successful in uncontrolled trials, it did not show benefit in controlled trials (a common outcome). Why not? Perhaps precisely because what works for one person may not work for another. Muddy thinking here—yet controlled trials remain the “gold standard.” Even an autist like me can see the flaw in such reasoning.
Peter Good
Autism Studiespetergood1@mac.com

The secretin example is a very bad one. No autistic child was tested for secretin defficiency in those trials and no clinical testing was done to know about other biochemical, metabolic, immune or and gastrointestinal problems who could mask any benefit.
Even more, with the new research on secretin and oxytocin, the conclussions are not up to date to the new knowledge on the topic.

Thank you to AS for making this meeting available on the web. It is greatly appreciated by parents like myself who may only have time to watch these meetings in the evenings.

However I am having a horrible time logging on! I have an Apple. Why do we need to go through this strange Microsoft porthole that is asking me for account information regarding an account I do not have?????????????

I found this misleading. My now five year old had developmental issues accross the board and our pediatrician did not think he had Autism. He did receive EI, which gave him many therapies, however, non with the intensity he eventually received at age four. I beleive their is NO placebo that would help my child sleep…he was up all night for three years. I also believe their is no placebo that would help my child speak, and he is just now learning to label and say words.
It really implies that the issue is with the parent feeling more optimistic? I hope this is not what it implies.